{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:26:31Z","timestamp":1790141191382,"version":"4.0.1"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3286,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The actions of 13 general anaesthetics (diethyl ether, enflurane, isoflurane, methoxyflurane, sevoflurane, chloral hydrate, trifluoroethanol, tribromoethanol, <jats:italic>tert<\/jats:italic>\u2010butanol, chloretone, brometone, trichloroethylene, and \u03b1\u2010chloralose) were studied on agonist\u2010activated Cl<jats:sup>\u2212<\/jats:sup> currents at human GABA<jats:sub>A<\/jats:sub> \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>, glycine \u03b1<jats:sub>1<\/jats:sub>, and GABA<jats:sub>C<\/jats:sub> \u03c1<jats:sub>1<\/jats:sub> receptors expressed in human embryonic kidney 293 cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>All 13 anaesthetics enhanced responses to submaximal (EC<jats:sub>20<\/jats:sub>) concentrations of agonist at GABA<jats:sub>A<\/jats:sub> and glycine receptors, except \u03b1\u2010chloralose, which did not enhance responses at the glycine \u03b1<jats:sub>1<\/jats:sub> receptor. None of the anaesthetics studied potentiated GABA responses at the GABA<jats:sub>C<\/jats:sub> \u03c1<jats:sub>1<\/jats:sub> receptor.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Potentiation of submaximal agonist currents by the anaesthetics was studied at GABA<jats:sub>A<\/jats:sub> and glycine receptors harbouring mutations in putative transmembrane domains 2 and 3 within GABA<jats:sub>A<\/jats:sub> \u03b1<jats:sub>2<\/jats:sub>, \u03b2<jats:sub>1<\/jats:sub>, or glycine \u03b1<jats:sub>1<\/jats:sub> receptor subunits: GABA<jats:sub>A<\/jats:sub> \u03b1<jats:sub>2<\/jats:sub>(S270I)\u03b2<jats:sub>1<\/jats:sub>, \u03b1<jats:sub>2<\/jats:sub>(A291W)\u03b2<jats:sub>1<\/jats:sub>, \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>(S265I), and \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>(M286W); glycine \u03b1<jats:sub>1<\/jats:sub>(S267I) and \u03b1<jats:sub>1<\/jats:sub>(A288W). For all anaesthetics studied except \u03b1\u2010chloralose, at least one of the mutations above abolished drug potentiation of agonist responses at GABA<jats:sub>A<\/jats:sub> and glycine receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u03b1\u2010Chloralose produced efficacious direct activation of the GABA<jats:sub>A<\/jats:sub> \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub> receptor (a \u2018GABA\u2010mimetic\u2019 effect). The other 12 anaesthetics produced minimal or no direct activation of GABA<jats:sub>A<\/jats:sub> and glycine receptors. A non\u2010anaesthetic isomer of \u03b1\u2010chloralose, \u03b2\u2010chloralose, was inactive at GABA<jats:sub>A<\/jats:sub> and glycine receptors and did not antagonize the actions of \u03b1\u2010chloralose at GABA<jats:sub>A<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The implications of these findings for the molecular mechanisms of action of general anaesthetics at GABA<jats:sub>A<\/jats:sub> and glycine receptors are discussed.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 731\u2013743; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703087\">10.1038\/sj.bjp.0703087<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703087","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:46:01Z","timestamp":1106945161000},"page":"731-743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["The actions of ether, alcohol and alkane general anaesthetics on GABA<sub>A<\/sub> and glycine receptors and the effects of TM2 and TM3 mutations"],"prefix":"10.1111","volume":"129","author":[{"given":"Matthew D","family":"Krasowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil L","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15903.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/45.3.294"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199901000-00018"},{"key":"e_1_2_7_5_1","first-page":"291","article-title":"International union of pharmacology. 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